In experimental diabetes the decrease in the eye of lens carnitine levels is an early important and selective event.

Carnitine is present in the eye tissues of the rabbit and the highest concentration is found in the lens. In streptozotocin-diabetic rats, the carnitine loss of the lens is an initial and important event. At 8 days after the induction of diabetes, the carnitine content in the rat lens was reduced by 63% compared to control. The loss of lens carnitine continued at 15 and 45 days after the induction. Total carnitine level in the serum was diminished by 15 days, and the reduction in percentage term was much lower in comparison to the loss of lens carnitine. In the rabbit after alloxan-diabetes induction, there is an extensive loss of carnitine in the lens: -85% after 4 months. The carnitine levels in the other eye tissues seem substantially unaffected. The loss of lens carnitine was present even with an inconsistent hyperglycaemia. No difference was found in serum carnitine levels between controls and alloxan-treated rabbits. The role of carnitine in lens is still unclear, but its loss may be related to the appearance of cataract. A derivative of carnitine, acetylcarnitine, might prevent the processes involved in the formation of cataracts by a pharmacological action, as has been shown for aspirin.

Quaternary nitrogen compounds affect carnitine distribution in rats. Particular emphasis on edrophonium.

Edrophonium (ethyl(m-hydroxyphenyl)dimethylamine) acutely modifies carnitine levels in different rat tissues, increasing hepatic and reducing blood and renal levels. After 2 h edrophonium treatment, the total serum carnitine levels were decreased by 16 (P < 0.001) and 33 (P < 0.001) percent in fed and fasted rats respectively compared to control, and in kidney the levels decreased by 11 (P < 0.05) and 34 (P < 0.001) percent whereas in liver the edrophonium treatment increased the levels by 43 (P < 0.001) and 59 (P < 0.001) percent. The edrophonium action does not depend on the route of administration or on the nutritional state of the animal. Its activity on carnitine levels is neither accompanied by significant variation of serum parameters of carbohydrate, fat and protein metabolism nor of insulin levels. The edrophonium activity is not related to cholinergic action, as physostigmine and ambenonium at concentrations known to increase cholinergic activity do not modify carnitine distribution in tissues. Trimethylphenylammonium (TPA) and trimethyl(p-aminophenyl)ammonium (TPA.NH2), compounds structurally similar to edrophonium, are on the contrary active on levels of carnitine and this effect is not related to their cholinergic potency. In 24 h fasted rats after the TPA and TPA. NH2 treatment, the total serum carnitine levels were decreased by 32 (P < 0.001) and 13 (n.s.) percent respectively compared to control, and in kidney the levels decreased by 15 (P < 0.02) and 5 (n.s.) percent, whereas in liver the treatment increased the levels by 72 (P < 0.001) and 45 (P < 0.01) percent. Moreover atropine, an acetylcholine antagonist, affects carnitine distribution in a way similar to edrophonium. Edrophonium activity on carnitine distribution, probably affects (inter)cellular carnitine transport by direct action on plasma membrane. Effect on capillary endothelium may be responsible for its observed action on muscle contraction force in imminent ischemia.

Alteration of tissue carnitine content following anaesthesia with barbiturate and surgery in rat.

The hypercatabolic state leads to urinary carnitine loss. Anaesthesia and surgical intervention causes stress conditions. The stress is accompanied by the alteration of hormone states and energy processes. Carnitine, which physiologically promotes the fatty acid metabolism and so plays a very important role for the heart, can be involved in these alterations. The aim of this study was to examine the effects of anaesthesia and surgical intervention on carnitine distribution in the tissues. Rats were anaesthetized with thiopental and surgical intervention was performed on the femoral artery and vein. Carnitine levels, as well as parameters indicative of energy metabolism, were measured in the blood and tissues. It was found that anaesthesia and surgical intervention increased the corticosterone levels in blood and decreased the carnitine levels in blood and kidney. Carnitine accumulated in the liver, whereas in heart and skeletal muscle it was redistributed by a decrease in the acylated form and an increase in the free form. Glycogen was accumulated in cardiac and skeletal muscle. Compared to anaesthesia, the surgical intervention increased glycogen storage and carnitine redistribution in heart and skeletal muscle. Moreover, it caused a decrease in cholesterol and an increase in urea in the blood. The fall in blood and kidney carnitine levels indicates a possible depletion of carnitine. The deacylation of carnitine in heart and skeletal muscle represents an important alteration in heart and muscle energetic metabolism. The increase in urea is a consequence of high proteolysis. Acylcarnitine administration during pre- and operative step might prevent the loss of carnitine, promoting the heart energetic metabolism and reducing the proteolysis. Moreover, in accordance with a recent interpretation of carnitine action as a membrane-stabilizing agent, the acylcarnitine supply could reduce the risk of "oedema" that follows the anaesthesia and surgical intervention.